System-wide transcriptome damage and tissue identity loss in COVID-19 patients

The molecular mechanisms underlying the clinical manifestations of COVID-19 and what distinguishes them from common seasonal influenza virus and other lung injury states such as Acute Respiratory Distress Syndrome, remains poorly understood. To address these challenges, we combine transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues to define body-wide transcriptome changes in response to COVID-19. We then match this data with spatial protein and expression profiling across 357 tissue sections from 16 representative patient lung samples and identify tissue compartment-specific damage wrought by SARS-CoV-2 infection, evident as a function of varying viral loads during the clinical course of infection and tissue type specific expression states. Overall, our findings reveal a systemic disruption of canonical cellular and transcriptional pathways across all tissues, which can inform subsequent studies to combat the mortality of COVID-19 and to better understand the molecular dynamics of lethal SARS-CoV-2 and other respiratory infections.


Other Contributors

Jiwoon Park,
Jonathan Foox,
Tyler Hether,
David C. Danko,
Sarah Warren,
Youngmi Kim,
Jason Reeves,
Daniel J. Butler,
Christopher Mozsary,
Joel Rosiene,
Alon Shaiber,
Evan E. Afshin,
Matthew MacKay,
André F. Rendeiro,
Yaron Bram,
Vasuretha Chandar,
Heather Geiger,
Arryn Craney,
Priya Velu,
Ari M. Melnick,
Iman Hajirasouliha,
Afshin Beheshti,
Deanne Taylor,
Amanda Saravia-Butler,
Urminder Singh,
Eve Syrkin Wurtele,
Jonathan Schisler,
Samantha Fennessey,
André Corvelo,
Michael C. Zody,
Soren Germer,
Steven Salvatore,
Shawn Levy,
Shixiu Wu,
Nicholas P. Tatonetti,
Sagi Shapira,
Mirella Salvatore,
Lars F. Westblade,
Melissa Cushing,
Hanna Rennert,
Alison J. Kriegel,
Olivier Elemento,
Marcin Imielinski,
Charles M. Rice,
Alain C. Borczuk,
Cem Meydan,
Robert E. Schwartz,
Christopher E. Mason